Using the analytic hierarchy process to support teams in defining new product objectives

Defining new product objectives is a critical problem solving activity to new product success. The analytic hierarchy process appears to be an adequate technique for multi-criteria decision analysis to support the definition of new product objectives. To illustrate this support, we applied this technique to a project focused on the development of a liver perfusion system to preserve donor livers. It quantitatively supported discussions between technological developers and clinical practitioners focused on the product requirements and the pursued performance of the liver perfusion system relative to an envisaged competitor. The discussions significantly reduced disagreements about the new product objectives between the group members. They resulted in a quantitative overview of the importance of the product requirements and the relative performance of the alternatives with regard to these requirements. Furthermore, research activities necessary to fulfil these objectives were discerned. The group members were committed to these outcomes. This application shows the value of introducing the AHP as a means to steer new products to solve problems to a higher extent than competing products do

Septal ablation in hypertrophic obstructive cardiomyopathy improves systolic myocardial function in the lateral (free wall): a follow-up study using CMR tissue tagging and 3D strain analysis

Aims: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis. Methods and results: In nine patients (age 52±15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72±27 to 59±21 g; P=0.008 and from 131±34 to 109±30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5±21.1 to -70.0±16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9±2.8 to -18.8±3.2%; P=0.02 and from -70.3±9.2 to -86.1±15.0%/s; P=0.01, respectively). Conclusion: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling. © The European Society of Cardiology 2006. All rights reserved

Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced thermogenesis

The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the ß-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the ß2-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26·7(SEM 0·8) kg/m2; age 45·2(SEM1·4) years) with different polymorph-isms of the ß2-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between poly-morphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P,0·05). The ß2-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the ß2-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermo-genic response to the meal was correlated with variations in the plasma adrenaline response to the meal. ß2-Adrenoceptor polymorphisms: Diet-induced thermogenesis: Catecholamines Energy expenditure (EE) is an important factor in body-weight regulation. Diet-induced thermogenesis (DIT) is the EE associ-ated with ingestion, absorption and storage of food and account

Impact of alcohol septal ablation on left anterior descending coronary artery blood flow in hypertrophic obstructive cardiomyopathy

Objectives: The aim of this study was to evaluate the effects of alcohol septal ablation (ASA) on coronary blood flow in symptomatic hypertrophic obstructive cardiomyopathy (HOCM) using cardiac MR (CMR) coronary flow measurements. Background: CMR flow mapping enables quantification of coronary blood flow in a noninvasive way. Both left ventricular outflow tract (LVOT) gradient reduction and myocardial scarring after ASA are expected to influence left anterior descending (LAD) coronary blood flow. Methods: Cine, contrast-enhanced (CE) imaging and breath-hold CMR phase contrast velocity mapping were performed at baseline and 1 and 6 months after ASA in seven patients. Changes of coronary blood flow were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LVOT gradient reduction, and LV rate pressure product (LVRPP). Results: A significant mass reduction was observed bothin the target septal myocardium and in the total myocardium (both P < 0.01). Mean myoca

Diagnostic performance of early increase in S100B or LDH as outcome predictor for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma

As a subset of advanced melanoma patients derive long-term benefit from anti-PD-1 therapy, early identification of non-responsiveness would enable an early switch to next line therapies. This study assessed if an early increase in S100B or lactate dehydrogenase (LDH) could be predictive for non-responsiveness to anti-PD-1. We retrospectively analysed advanced melanoma patients treated with anti-PD-1 monotherapy. Serum S100B and LDH levels were measured at baseline and before every infusion. Non-response was defined as progression or death at 6 months. Marker cut-offs were defined based on > 95% specificity and feasibility in clinical practice. For validation an independent cohort was analysed. In total, 313 patients were included (166 patients in training cohort, 147 patients in validation cohort). Increase of > 50% in LDH or > 100% in S100B above upper limit of normal at week 6 compared to baseline was determined as criterion to positively test for non-responsiveness. In the validation cohort, obtained specificity of the combination test was > 95% with a positive predictive value of 82%; obtained sensitivity was lower (21%), with a negative predictive value of 55%. Early increase in S100B or LDH is a strong parameter for non-responsiveness to anti-PD-1 in advanced melanoma. Prospective confirmation is needed before clinical implementation.</p

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: Initial 3-months results of the BeSt for Kids-study

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. Methods: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. Results: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. Conclusion: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. Trial registration:NTR1574. Registered 3 December 2008

TomograPy: A Fast, Instrument-Independent, Solar Tomography Software

Solar tomography has progressed rapidly in recent years thanks to the development of robust algorithms and the availability of more powerful computers. It can today provide crucial insights in solving issues related to the line-of-sight integration present in the data of solar imagers and coronagraphs. However, there remain challenges such as the increase of the available volume of data, the handling of the temporal evolution of the observed structures, and the heterogeneity of the data in multi-spacecraft studies. We present a generic software package that can perform fast tomographic inversions that scales linearly with the number of measurements, linearly with the length of the reconstruction cube (and not the number of voxels) and linearly with the number of cores and can use data from different sources and with a variety of physical models: TomograPy (http://nbarbey.github.com/TomograPy/), an open-source software freely available on the Python Package Index. For performance, TomograPy uses a parallelized-projection algorithm. It relies on the World Coordinate System standard to manage various data sources. A variety of inversion algorithms are provided to perform the tomographic-map estimation. A test suite is provided along with the code to ensure software quality. Since it makes use of the Siddon algorithm it is restricted to rectangular parallelepiped voxels but the spherical geometry of the corona can be handled through proper use of priors. We describe the main features of the code and show three practical examples of multi-spacecraft tomographic inversions using STEREO/EUVI and STEREO/COR1 data. Static and smoothly varying temporal evolution models are presented.Comment: 21 pages, 6 figures, 5 table

How spiking neurons give rise to a temporal-feature map

A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells’ synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity

Psychometric properties of the pediatric patient-reported outcomes measurement information system item banks in a Dutch clinical sample of children with juvenile idiopathic arthritis

Objective To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA).Methods A total of 154 Dutch children (mean +/- SD age 14.4 +/- 3.0 years; range 8-18 years) with JIA completed 8 pediatric version 1.0 PROMIS item banks (anger, anxiety, depressive symptoms, fatigue, pain interference, peer relationships, physical function mobility, physical function upper extremity) twice and the Pediatric Quality of Life Inventory (PedsQL) and the Childhood Health Assessment Questionnaire (C-HAQ) once. Structural validity of the item banks was assessed by fitting a graded response model (GRM) and inspecting GRM fit (comparative fit index [CFI], Tucker-Lewis index [TLI], and root mean square error of approximation [RMSEA]) and item fit (S-X-2 statistic). Convergent validity (with PedsQL/C-HAQ subdomains) and discriminative validity (active/inactive disease) were assessed. Reliability of the item banks, short forms, and computerized adaptive testing (CAT) was expressed as the SE of theta (SE[theta]). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) and smallest detectable change.Results All item banks had sufficient overall GRM fit (CFI >0.95, TLI >0.95, RMSEA 0.001). High correlations (>0.70) were found between most PROMIS T scores and hypothesized PedsQL/C-HAQ (sub)domains. Mobility, pain interference, and upper extremity item banks were able to discriminate between patients with active and inactive disease. Regarding reliability, PROMIS item banks outperformed legacy instruments. Post hoc CAT simulations outperformed short forms. Test-retest reliability was strong (ICC >0.70) for all full-length item banks and short forms, except for the peer relationships item bank.Conclusion The pediatric PROMIS item banks displayed sufficient psychometric properties for Dutch children with JIA. PROMIS item banks are ready for use in clinical research and practice for children with JIA.Transplantation and immunomodulatio